This study proposes to better understand the central factors involved in the etiopathogenesis of altered pain perception in fibromyalgia (FM). We test six hypotheses drawn from a model which posits that neuroendocrine and immunologic abnormalities, characterized by decreases in cerebrospinal fluid (CSF) serotonin and increases in CSF substance P (SP), lead to sensitization of central nervous system structures involved in pain perception, i.e. thalamus and caudate nucleus. We have completed data collection on seven patients with fibromyalgia and six healthy controls. Analyses of these preliminary data reveal that, consistent with our previously published findings, patients with FM, relative to healthy controls, exhibit significantly lower pain threshold levels and significantly lower regional cerebral blood flow (rCBF) to the thalamus and caudate nucleus. The patients who are characterized by significantly higher cerebrospinal fluid (CSF) levels of substance P. The correlation between rCBF and substance P in the patients is .91 (p=.004) in the caudate nucleus and .82 (p=.02) in the thalamus. These preliminary data suggest that low rCBF in the thalamus and caudate nucleus may be the product of a compensatory response to high nociceptive input marked by high CSF substance P. That is, the thalamus and caudate nucleus may inhibit functional activity to modulate the amount of nociceptive transmission that reaches higher brain structures where perceptions of pain are organized.